Dengue Fever: Endemic to Epidemic

Today, a bite from the wrong mosquito can cause severe fever, organ failure, and even death. No, this mosquito is not carrying malaria as you may have thought, it is carrying dengue. According to the World Health Organization (WHO), dengue fever is a viral infection carried by female mosquitoes of the species Aedes aegypti (Ae. aegypti), the same species responsible for transmitting diseases such as yellow fever and Zika. Infection causes symptoms similar to that of the flu, and can be lethal if it develops into “severe dengue.” Currently, severe dengue is one of the most common causes of illness and death in many Asian and Latin American countries. 1 Dengue is unique because it has no known treatment and prevention relies solely on mosquito vector control. Despite these difficulties, early detection of the virus and standard medical care brings fatality rates under 1%.1 Although the recent resurgence of dengue fever is extremely complex and involves many interconnected external factors, there are four major probable causes of the global spread of the disease: increased urbanization, higher rates of international trade and travel, poor vector control, and global climate change.

The first documented case of dengue-like symptoms dates back to the Chinese Jin Dynasty (265-420 AD) with a Chinese encyclopedia description of a “water poison” carried by flying insects.2 The disease was not identified and named until 1779, and was immediately followed by simultaneous epidemics in Asia, Africa, and North America in the 1780s. In 1789, the first confirmed case report of definite dengue symptoms came to light. The author, Benjamin Rush, coined the term “breakbone fever” due to the symptoms of myalgia (muscle pain) and arthralgia (joint pain). 2 Yet despite more frequent occurrences of the fever, it was not until the 20th century that the causes and transmission of the disease were uncovered.2 Since then, a combination of complex economic, social, and environmental factors has led to a massive spread of dengue across more than 100 countries, including a concerning resurgence in the most recent decades. In the past 50 years, rates of dengue have increased 30 times over.3 Currently, experts estimate there are approximately 390 million annual dengue infections and 3.9 billion people at risk of infection globally.1

A city view of Dhaka, Bangladesh. Source: Rio Plus Centre.

At the heart of the current dengue crisis is the climbing rate of urbanization. In 1950, less than one-third of the world’s population lived in urban areas.4 The year 2007 was the first year that the global urban population was greater than the global rural population, and as of 2014, 54 percent of Earth’s population resided in urban areas.4 This phenomenon is expected to continue; the UN estimates that by 2050, the global population will be two-thirds urban and one-third rural.4 This urbanization provides the perfect niche for the Ae. aegypti vector to flourish. The development of “urban port cities” allows the mosquito to establish and adapt itself to the human population. Although the mosquito originally bred in small, natural stationary bodies of water, Ae. aegypti now proliferates in extremely small bodies of water created by urban living, such as water in discarded trash, bottles, plastic, and tires. In addition, water storage containers in areas that lack clean running water provide a convenient breeding ground for the mosquito.

Furthermore, Ae. aegypti has adapted to prefer indoor living to the outside world, and favors humans rather than other animals for feeding. Duane Gubler, director of the Asia-Pacific Institute of Tropical Medicine and Infectious Diseases at the University of Hawaii at Manoa in Honolulu, believes this acclimatization makes Ae. aegypti “perfectly adapted to the urban environment.”3 Urbanization also provides optimal conditions for Ae. aegypti to thrive on a smaller scale. Cramped living spaces, poor public sanitation of water, sewage, and waste, and substandard housing provide a wealth of opportunity for Ae. aegypti to succeed. The effects of this have been seen already: the rapid economic growth and urbanization of southeast Asia post-World War II provided ideal conditions for a dengue epidemic. The virus’s progression during this time reached a tipping point and led to the first reports of dengue hemorrhagic fever (DHF), a much more severe and lethal form of the disease that is accompanied by hemorrhaging and often death.3 DHF has spread exceptionally far since this first introduction; current WHO estimates hover around half a million cases and 22,000 deaths due to DHF each year, largely among children.3 Today’s rapid urbanization has the potential to lead to the spread of severe forms of dengue and even greater specialization of Ae. aegypti to humans.

Another one of the biggest propellers of the global spread of dengue is increased air travel and trade across international borders. In 1980, approximately 227 million people crossed international borders via airplanes.5 As of 2012, that number had risen to over a billion people per year, and according to the UN World Tourism Organization (WTO), could reach 1.8 billion international tourist arrivals by 2030.5 This movement of people and goods to new regions allows dengue to grow at unprecedented rates by allowing different dengue strains to come in contact with each other frequently. In turn, this sharply increases the risk of developing the more severe DHF, which is often accompanied by a higher mortality rate, a phenomenon that has been seen multiple times throughout the history of the disease. Most recently this occurred in 1981 when a strain of dengue was imported from southeast Asia. This led to the first DHF outbreak and eventual epidemic in the America. Following the introduction of the first strain, all four strains of dengue have since spread throughout the Americas and are now endemic in several countries.3 As rates of international air travel continue to skyrocket, it is likely that they will play an increasingly larger role in the global spread and resurgence of dengue.

One of the greatest difficulties regarding the control of dengue is the lack of any cure, vaccine, or even treatment of the disease. Currently, the only mechanism for control is managing the vector, Ae. aegypti, and poor vector control is one of the most prominent flaws in the effort to eradicate dengue. According to the WHO, control of the vector is achieved by “eliminating container habitats” that lend themselves to the laying or depositing of vector eggs and facilitate the development of aquatic stages.6 Based on a number of factors, including local ecology, resources available, and cultural context, methods of control can include a host of different tactics, such as biological agents, adulticides, larviciding with insecticides, and elimination of larval habitats.6 However, recent research has shown that often generalized “clean-up campaigns” and application of pesticides have a limited or even negligible effect on rates of dengue incidence.7 Even in cases where eradication efforts have been successful, there are often higher levels of cases once the effort shrinks or comes to a halt altogether. This can be seen in the virtual elimination of dengue in the Americas due to yellow fever eradication efforts of the 1950s and 1960s. The Pan American Health Organization (PAHO) targeted Ae. aegypti (which also transmits yellow fever) with DDT. In 1972, DDT was banned in the US and the Ae. aegypti elimination effort was deemed successful.3 The effort was subsequently abandoned as President Nixon turned his attention to the “War on Cancer.” Today, Ae. aegypti has reinfested almost every region from which it was eliminated.3 The public health infrastructure needed to combat this complex disease has declined in the past 30 years, largely due to competing global health issues and limited resources. Currently, many countries’ approach to vector-borne diseases are “end of the pipe solutions,” working to respond to epidemics by implementing emergency control measures, rather than prevention programs.8 In order to effect serious change in the rates of dengue incidence, vector control measures that are both effective and consistent over time will need to be put in place.

A child stands next to a rainwater tank full of stationary water. Source: Water Journalists Africa.

Arguably the most highly-contested cause of dengue dissemination is global climate change. Research has consistently shown that there is a clear weather-related pattern involved with dengue fever. Higher rainfall and temperatures correlate with higher rates of vector spread and likelihood of virus transmission to humans. These rates go down in cooler climates due to the length of virus replication. According to senior research fellow Simon Hales at the University of Otago, New Zealand, it is probable that in cooler climates, the time it takes to replicate the virus would exceed the lifespan of Ae. aegypti, meaning the mosquito would likely die before transmission to humans. Accordingly, many research studies predict that the future of the Earth’s climate will increase the risk and frequency of dengue epidemics.3 The UN Intergovernmental Panel on Climate Change’s Fourth Assessment Report on Climate Change Impacts: Impacts, Adaptation and Vulnerability concludes that climate change could increase the populations at risk for dengue due to environmental variable such as “El Niño, temperature, rainfall and cloud cover.”3 Despite this, researchers are divided on the causal relationship between climate change and dengue. Some experts, such as Laura Harrington, a medical entomologist at Cornell University, disagrees with those who say global warming is a clear cause of the spread of dengue.3 She and many others argue that climate change may influence dengue indirectly in its impact on water transport and management, but none of the climate data points to a direct link between climate change affecting rates of dengue incidence. Additionally, some researchers contend that policy-makers use global warming as a political tool to account for the lack of prevention of a very controllable disease.3 Ultimately, the science behind climate change and all of its impacts has yet to be explored fully, but it is clear that the climate and weather patterns play at least some role in the distribution of dengue fever globally.

Despite the lack of knowledge about dengue and the many facets of such a complicated disease, many relief efforts are promising. Research involving every element of the dengue virus continues to add to the scientific body of information we can use to combat the spread of this disease. Mathematical models are being developed that are working towards predictions and simulations that may aid in the challenge of multiple strains infecting the same region and may support development of immunizations for the disease. Additionally, the Grand Challenges in Global Health program is working towards creating genetically modified vectors that would be unable to transmit dengue to humans. All of these efforts will push towards the reduction of dengue, but ultimately much of the research leads to similar conclusions: the disease will eventually require a vaccine. Ongoing research at the Pediatric Dengue Vaccine Initiative is working to overcome the obstacles of vaccine development by aiding companies with clinical trials, field research, and establishing health infrastructure for eventual vaccine dissemination.3 As the fields of science, global health, and policymaking move forward, the world will look forward to a dengue-free future.

Sarah Spaulding is a junior in Jonathan Edwards College from Wilmington, North Carolina double majoring in Environmental Engineering and Ecology & Evolutionary Biology. She can be contacted at sarah.spaulding@yale.edu.